HEMATOPOIETIC GROWTH FACTORS, ONCOGENES, AND LEUKEMIA

造血干细胞的生长和分化依赖于 造血生长因子1，2.1分泌蛋白的活性 白血病发生研究的中心问题之一是相互作用如何 这些生长因子中的一种在白血病细胞中发生改变。最近，有两个 人多能生长因子、人GM-CSF1和IL-3 分子克隆使蛋白质产物能够很容易地纯化到 同质性。这两个因素都支持 多种红系和髓系的造血干细胞 血统1，2。另一方面，白血病细胞对 生长因子与分化无关(67)。我们最近做了 显示癌基因c-myb的结构性表达可预防DMSO Friend小鼠红白血病(FMEL)细胞的诱导分化在……里面 此外，c-myb被认为是一种促进造血的有丝分裂原。 祖细胞(7)。我们将分析c-myb是否参与有丝分裂。 对IL-3和GM-CSF的反应。正常的造血祖细胞 将c-myb基因导入细胞，观察这种解离生长因子是否诱导 从分化中成长。此外，参与有丝分裂的基因 将确定对GM-CSF和IL-3的反应。因为荷尔蒙 与受体的相互作用是我们理解GM-CSF和 IL-3对细胞的影响，构建了一种独特的cDNA克隆载体 从分子上克隆各自的受体。这是一个值得研究的理想系统。 参与生长因子刺激的分子事件，以及 这些事件是如何在白血病细胞中改变的。

The growth and differentiation of hematopoietic stem cells dependent on the activities of secreted proteins termed hematopoietic growth factors 1,2. One of the central issues in the study of leukemogenesis is how the interactions of theses growth factors is altered in the leukemic cell. Recently, two human pluripotent growth factors, human GM-CSF1 and IL-3 have been molecularly cloned enabling the protein product to be easily purified to homogeneity. Both of these factors support the growth and differentiation of a wide variety of hematopoietic stem cells of both erythroid and myeloid lineages 1,2. On the other hand, leukemic cell proliferation in response to growth factors is dissociated from differentiation (67). We have recently shown that constitutive expression of the oncogene c-myb prevents DMSO induced differentiation of Friend Mouse Erythroleukemia (FMEL) cells. In addition, c-myb has been implicated as a mitogen for hematopoietic progenitors (7). We will analyze whether c-myb is involved in the mitogenic response to IL-3 and GM-CSF. Normal hematopoietic progenitors will be transfected with a c-myb to see if this dissociates growth factor induced growth from differentiation. In addition, genes involved in the mitogenic response to GM-CSF and IL-3 will be identified. Since the hormone interactions with receptor are essential in our understanding of GM-CSF and IL-3 effects on cells, a unique cDNA cloning vector has been constructed to molecularly clone the respective receptors. This is an ideal system to study the molecular events which are involved in growth factor stimulation, and how these events are altered in a leukemic cell.